The effect of ethnicity on outcome in systemic sclerosis (SSc) is not well understood. The hypothesis to be tested in this proposal is that SSc is a more aggressive disease in non-Caucasians, who manifest a higher occurrence of critical organ involvement and a worse prognosis, and that reasons for this may include genetic factors as well as sociodemographic or behavioral determinants.Therefore, we will: 1) select a well-defined cohort of Caucasians, Hispanics and African Americans (approximately 80 Caucasians 40-50 African Americans and 40-50 Hispanics) with SSc of five years or less in duration from SSc patients seen at three southern Texas medical centers in order to ascertain their initial status and follow their course and early outcome at regular intervals for a period of at least three years; 2) determine the HLA class II genotypes (HLA-DRB1, DQA1, DQB1 and DPB1 alleles) as well as disease-associated alleles of other candidate genes found to be associated with SSc (e.g. fibrillin, Interleukin 1 receptor antagonist (IL-1-RA), DNA topoisomerase I and others): 3) determine the sociodemographic parameters of these patients. 4) determine pertinent clinical and laboratory parameters, including disease manifestations, laboratory features and selected SSc-associated autoantibodies (anti- centromere antibodies (ACA), antitopoisomerase I (anti-topo I) anti- fibrillarin (anti-fib), etc , whose expression has been shown to be associated with specific clinical features of SSc as well as with certain HLA class II alleles: 5) follow disease progression to outcomes as manifested by: a) the development of end-stage pulmonary fibrosis b) end-stage scleroderma-related renal disease; c) scleroderma heart disease, d) scleroderma-related gastrointestinal involvement; e) MD global assessment of disease severity; f)functional disability; or g) death; 6) examine the relative contributions and interactions of genetic demographic, socioeconomic, cultural. and initial clinical and laboratory features on the course and outcome of early SSc. Elucidation of those factors affecting outcome in SSc will not only permit modification thereof, but also the identification of high-risk patients to whom earlier and more aggressive therapy could be rendered. which may ultimately improve the prognosis of this disease.